VIRULENCE IN ENTEROAGGREGATIVE E COLI

Summary

Principal Investigator: James Nataro
Affiliation: University of Maryland
Country: USA
Abstract: Enteroaggregative Escherichia coli (EAEC) is an increasingly recognized pathogen of human diarrhea. This organism has been implicated in sporadic diarrhea in developing and industrialized countries, in the persistent diarrhea syndrome in AIDS patients and children in the developing world, in traveler's diarrhea, and in various diarrheal outbreaks. The PI discovered this pathotype of diarrheagenic E. coli and has been the leader in describing the pathogenesis and epidemiology of this organism, This is a competing continuation of our fundamental work on the pathogenesis of EAEC infection. Overall, our objectives are to advance knowledge of EAEC pathogenesis, to better define true EAEC pathogens, to refine diagnostic methods and to identify protective immunogen. The three aims of this proposal seek to extend the most important and promising aspects of the work funded under the current award. Aim 1: Characterization of EAEC adhesion-Aggregation is the defining characterization of EAEC. Our observations suggest that aggregative adherence (AA) is a prelude to biofilm formation, which occurs in vivo and which can be modeled in vitro. In this aim, we will further elucidate fundamental aspects of EAEC adherence. Aim 2: The Regulation of EAEC virulence- AggR is a highly prevalent and conserved activator of AAF expression. However, nothing else is known of the regulation of EAEC virulence. Beginning with AggR, we will expand our studies of EAEC gene regulation. Aim 3: Reconstructing EAEC-We will use in vitro organ culture and T84 cell models of EAEC infection to answer the question: what genes are necessary and sufficient to confer the effects that we observe? The work under this award will greatly advance the current state of knowledge of EAEC and will result in the identification of pathogenetic mechanisms, of diagnostic reagents and in vaccine candidates.
Funding Period: 2000-08-01 - 2005-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Enteroaggregative Escherichia coli: surface protein dispersin increases bacterial uptake of ciprofloxacin
    Ninell P Mortensen
    Biological and Nanoscale Systems Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA Center for Aerosol and Nanomaterials Engineering, RTI International, Research Triangle Park, NC 27709, USA
    Int J Antimicrob Agents 42:462-5. 2013
  2. pmc Bacterial serine proteases secreted by the autotransporter pathway: classification, specificity, and role in virulence
    Fernando Ruiz-Perez
    Department of Pediatrics, School of Medicine, University of Virginia, P O Box 800326, MR4 Room 4012C, 409 Lane Road, Charlottesville, VA, 22908, USA
    Cell Mol Life Sci 71:745-70. 2014
  3. pmc Enteroaggregative Escherichia coli strain in a novel weaned mouse model: exacerbation by malnutrition, biofilm as a virulence factor and treatment by nitazoxanide
    David T Bolick
    Center for Global Health, Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA
    J Med Microbiol 62:896-905. 2013
  4. pmc Enteroaggregative Escherichia coli disrupts epithelial cell tight junctions
    Maura C Strauman
    The Wistar Institute, Philadelphia, Pennsylvania, USA
    Infect Immun 78:4958-64. 2010
  5. pmc Enteroaggregative Escherichia coli quantification in children stool samples using quantitative PCR
    Ila Fernanda Nunes Lima
    Institute of Biomedicine for Brazilian Semi Arid IBISAB and Clinical Research Unit, Federal University of Ceara, Fortaleza, Ceara, Brazil
    APMIS 121:643-51. 2013
  6. pmc Characterization of the AggR regulon in enteroaggregative Escherichia coli
    Nicholas Morin
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Infect Immun 81:122-32. 2013
  7. pmc The fimbriae of enteroaggregative Escherichia coli induce epithelial inflammation in vitro and in a human intestinal xenograft model
    Erik J Boll
    Department of Microbiological Surveillance and Research, Statens Serum Institut, Denmark
    J Infect Dis 206:714-22. 2012
  8. pmc Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany
    David A Rasko
    University of Maryland School of Medicine, Institute for Genome Sciences and Department of Microbiology, Baltimore, USA
    N Engl J Med 365:709-17. 2011
  9. pmc Serine protease autotransporters from Shigella flexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins
    Fernando Ruiz-Perez
    Center for Vaccine Development and Program of Comparative Medicine, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Proc Natl Acad Sci U S A 108:12881-6. 2011
  10. pmc Shigella enterotoxin-2 is a type III effector that participates in Shigella-induced interleukin 8 secretion by epithelial cells
    Mauricio J Farfan
    Centro de Estudios Moleculares, Departamento de Pediatria, Hospital Luis Calvo Mackennna, Facultad de Medicina, Universidad de Chile, Santiago, Chile
    FEMS Immunol Med Microbiol 61:332-9. 2011

Scientific Experts

  • Mauricio J Farfan
  • Fernando Ruiz-Perez
  • Claudine Irles
  • James P Nataro
  • Nadia Boisen
  • Karen A Krogfelt
  • Ila Fernanda Nunes Lima
  • Nicholas Morin
  • Ninell P Mortensen
  • David T Bolick
  • Erik J Boll
  • Carsten Struve
  • Renato E Cappello
  • David A Rasko
  • Flemming Scheutz
  • Maura C Strauman
  • David B Huang
  • M A Beckmann
  • Araceli E Santiago
  • David P Allison
  • Richard Littleton Guerrant
  • Richard L Guerrant
  • Robert K Ernst
  • James K Roche
  • Josiane da Silva Quetz
  • Alexandre Havt
  • Josep Bassaganya-Riera
  • Jason D Fowlkes
  • Aldo Angelo Moreira Lima
  • Stephen J Kennel
  • Sonia Carey
  • Raquel Hontecillas
  • Stacey J Guillot
  • Eric R Houpt
  • Mitchel J Doktycz
  • Anja Sander
  • Zachary Demma
  • Beth A McCormick
  • JOHN EID
  • Chen Shan Chin
  • Robert Sebra
  • James Bullard
  • Julia C Redman
  • Ellen E Paxinos
  • Andrew Kasarskis
  • Guadalupe Estrada-Gutierrez
  • Andreas M Petersen
  • Dimitris Iliopoulos
  • Jakob Frimodt-Møller
  • Andrey O Kislyuk
  • Ali Bashir
  • Robert J Bloch
  • Paul Peluso
  • Lawrence Lee
  • Susan R Steyert
  • David Rank
  • Jason W Sahl
  • Matthew K Waldor
  • Eric E Schadt
  • Aaron Klammer
  • Dale R Webster
  • Susanna Wang
  • Silvia Giono-Cerezo
  • Susan M Harrington
  • Erik Juncker Boll
  • Jill M Harper
  • Herbert L DuPont
  • Pablo C Okhuysen
  • Jamal A Mohamed
  • Zhi Dong Jiang
  • M J Doktycz
  • S Venkataraman
  • D P Allison
  • J P Nataro
  • C J Sullivan
  • J L Morrell-Falvey

Detail Information

Publications14

  1. ncbi Enteroaggregative Escherichia coli: surface protein dispersin increases bacterial uptake of ciprofloxacin
    Ninell P Mortensen
    Biological and Nanoscale Systems Group, Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA Center for Aerosol and Nanomaterials Engineering, RTI International, Research Triangle Park, NC 27709, USA
    Int J Antimicrob Agents 42:462-5. 2013
    ....
  2. pmc Bacterial serine proteases secreted by the autotransporter pathway: classification, specificity, and role in virulence
    Fernando Ruiz-Perez
    Department of Pediatrics, School of Medicine, University of Virginia, P O Box 800326, MR4 Room 4012C, 409 Lane Road, Charlottesville, VA, 22908, USA
    Cell Mol Life Sci 71:745-70. 2014
    ..Here, we discuss their classification, substrate specificity, and potential roles in pathogenesis. ..
  3. pmc Enteroaggregative Escherichia coli strain in a novel weaned mouse model: exacerbation by malnutrition, biofilm as a virulence factor and treatment by nitazoxanide
    David T Bolick
    Center for Global Health, Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA
    J Med Microbiol 62:896-905. 2013
    ....
  4. pmc Enteroaggregative Escherichia coli disrupts epithelial cell tight junctions
    Maura C Strauman
    The Wistar Institute, Philadelphia, Pennsylvania, USA
    Infect Immun 78:4958-64. 2010
    ..Our results show that EAEC induces epithelial barrier dysfunction in vitro and implicates the AAF adhesins in this phenotype...
  5. pmc Enteroaggregative Escherichia coli quantification in children stool samples using quantitative PCR
    Ila Fernanda Nunes Lima
    Institute of Biomedicine for Brazilian Semi Arid IBISAB and Clinical Research Unit, Federal University of Ceara, Fortaleza, Ceara, Brazil
    APMIS 121:643-51. 2013
    ..This new quantitative method provides a relatively simple means to quantify EAEC, which will likely be key to understanding the pathophysiology and impact of EAEC infection...
  6. pmc Characterization of the AggR regulon in enteroaggregative Escherichia coli
    Nicholas Morin
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA
    Infect Immun 81:122-32. 2013
    ..We show that mutations in these ORFs confer changes in bacterial surface properties. AggR coordinately controls expression of a large number of EAEC genes...
  7. pmc The fimbriae of enteroaggregative Escherichia coli induce epithelial inflammation in vitro and in a human intestinal xenograft model
    Erik J Boll
    Department of Microbiological Surveillance and Research, Statens Serum Institut, Denmark
    J Infect Dis 206:714-22. 2012
    ..Although previous studies report on the inflammatory aspects of EAEC pathogenesis, the mechanisms by which EAEC trigger these events are not well understood...
  8. pmc Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany
    David A Rasko
    University of Maryland School of Medicine, Institute for Genome Sciences and Department of Microbiology, Baltimore, USA
    N Engl J Med 365:709-17. 2011
    ..coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains, it should be classified within the enteroaggregative pathotype of E. coli...
  9. pmc Serine protease autotransporters from Shigella flexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins
    Fernando Ruiz-Perez
    Center for Vaccine Development and Program of Comparative Medicine, Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Proc Natl Acad Sci U S A 108:12881-6. 2011
    ..In the guinea pig keratoconjunctivitis model, a Shigella pic mutant induced greater inflammation than its parent strain. We suggest that the class-2 SPATEs represent unique immune-modulating bacterial virulence factors...
  10. pmc Shigella enterotoxin-2 is a type III effector that participates in Shigella-induced interleukin 8 secretion by epithelial cells
    Mauricio J Farfan
    Centro de Estudios Moleculares, Departamento de Pediatria, Hospital Luis Calvo Mackennna, Facultad de Medicina, Universidad de Chile, Santiago, Chile
    FEMS Immunol Med Microbiol 61:332-9. 2011
    ....
  11. pmc Effects of the plasmid-encoded toxin of enteroaggregative Escherichia coli on focal adhesion complexes
    Renato E Cappello
    Institutional Program in Molecular Biomedicine, National School of Homeopathy and Medicine, Instituto Politecnico Nacional, Mexico City, Mexico
    FEMS Immunol Med Microbiol 61:301-14. 2011
    ..Finally, we show that in vitro tyrosine-dephosphorylated FAK was susceptible to Pet cleavage. These data suggest that mechanisms other than spectrin redistribution occur during Pet intoxication...
  12. pmc Short report: high prevalence of serine protease autotransporter cytotoxins among strains of enteroaggregative Escherichia coli
    Nadia Boisen
    Department of Bacteriology, Mycology and Parasitology, Statens Serum Institut, Copenhagen, Denmark
    Am J Trop Med Hyg 80:294-301. 2009
    ..coli pathotypes rarely harbored a cytotoxic SPATE gene. SPATEs may be relevant to the pathogenesis of both EAEC and Shigella spp...
  13. ncbi Virulence characteristics and the molecular epidemiology of enteroaggregative Escherichia coli isolates from travellers to developing countries
    David B Huang
    Baylor College of Medicine, Division of Infectious Diseases, Houston, TX, USA
    J Med Microbiol 56:1386-92. 2007
    ....
  14. ncbi Measuring cell surface elasticity on enteroaggregative Escherichia coli wild type and dispersin mutant by AFM
    M A Beckmann
    UT ORNL Graduate School of Genome Science and Technology, The University of Tennessee, Knoxville, 37996 0840, USA
    Ultramicroscopy 106:695-702. 2006
    ..This work represents an initial step in efforts to understand the pathogenic role of the dispersin protein in the wild-type bacteria...